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Effects of nitric oxide synthase inhibitors on systemic hypotension, cytokines and inducible nitric oxide synthase expression and lung injury following endotoxin administration in rats.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Wang, Dapeng Wei, Jian-An Jau, Jack Lieu, M. W. Chao, T. J. Chen, Hsing I. |
| Copyright Year | 1999 |
| Abstract | Endotoxin shock is characterized by systemic hypotension, hyporeactiveness to vasoconstrictors and acute lung edema. A nitric oxide synthase (NOS) inhibitor, NG-monomethyl-L-arginine (L-NMMA) has been shown to be effective in reversing acute lung injury. In the present study, we evaluated the effects of NOS blockade by different mechanisms on the endotoxin-induced changes. In anesthetized rats, lipopolysaccharide (LPS, Klebsiella pneumoniae) was administered intravenously in a dose of 10 mg/kg. LPS caused sustained systemic hypotension accompanied by an eightfold increase of exhaled NO during an observation period of 4 h. After the experiment, the lung weight was obtained and lung tissues were taken for the determination of mRNA expressions of inducible NOS (iNOS), interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha-(TNF-alpha). Histological examination of the lungs was also performed. In the control group injected with saline solution, mRNA expressions of iNOS, IL-1beta and TNF-alpha were absent. Four hours after LPS, the mRNA expressions of iNOS and IL-1beta were still significantly enhanced, but TNF-alpha was not discernibly expressed. LPS also caused a twofold increase in lung weight. Pathological examination revealed endothelial damage and interstitial edema. Various NOS inhibitors were given 1 h after LPS administration. These agents included Nomega-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg), a constitutive NOS and iNOS inhibitor; S, S'-1,4-phenylene-bis-(1,2-ethanedinyl) bis-isothiourea dihydrobromide (1,4-PBIT, 10 mg/kg), a relatively specific iNOS inhibitor, and dexamethasone (3 mg/kg), an inhibitor of iNOS expression. These NOS inhibitors all effectively reversed the systemic hypotension, reduced the exhaled NO concentration and prevented acute lung injury. The LPS-induced mRNA expressions of iNOS and IL-1beta were also significantly depressed by these NOS inhibitors. Our results suggest that NO production through the iNOS pathway is responsible for endotoxin-induced lung injury. Certain cytokines such as IL-1beta are possibly involved. These changes are minimized by NOS inhibitors through different mechanisms. |
| Starting Page | 28 |
| Ending Page | 35 |
| Page Count | 8 |
| File Format | PDF HTM / HTML |
| DOI | 10.1007/BF02256421 |
| PubMed reference number | 9933740 |
| Journal | Medline |
| Volume Number | 6 |
| Issue Number | 1 |
| Alternate Webpage(s) | https://page-one.live.cf.public.springer.com/pdf/preview/10.1007/BF02256421 |
| Journal | Journal of biomedical science |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
